Francis, forced to abandon Lombardy after the French defeat at the Battle of Bicocca in 1522 and determined to regain possession of the territory, had ordered an invasion of the region in late 1523, with an army of eighteen thousand men under the command of Guillaume Gouffier, Seigneur de Bonnivet.

The younger brother of Artus Gouffier, seigneur de Boisy, tutor of Francis I of France, Bonnivet had been brought up with Francis, and after the young king's accession had became one of the most powerful of the royal favorites.

In 1515 he was made admiral of France.

In the imperial election of 1519 he superintended the candidature of Francis, and spent vast sums of money in his efforts to secure votes, but without success.

An implacable enemy of the Constable de Bourbon, he has contributed to the downfall of the latter.

In command of the army of Navarre in 1521, he had occupied Fuenterrabia and was probably responsible for the renewal of hostilities resulting from its not being restored.

Bonnivet had succeeded Odet de Foix, Vicomte de Lautrec, in 1523, as commander of the army of Italy.

The French army advances through the Piedmont to Novara, where it is joined by a similarly sized force of Swiss mercenaries.

Prospero Colonna, whose health is declining, has only nine thousand men to oppose the French advance, and finally decides to retreat to Milan.

Bonnivet, however, overestimates the size of the Spanish-Imperial army and moves into winter quarters rather than attacking the city.

This allows the commanders of Emperor Charles to summon fifteen thousand landsknechts and a large Spanish force under the command of Charles of Bourbon.

By December 28, when Charles de Lannoy replaces Colonna, Bonnivet has begun his withdrawal.

A member of the noble de Lannoy family, Charles was born the younger son of Jean de Lannoy, Lord of Mingoval, himself nephew of Jean III de Lannoy.

His mother was Philipotte de Lalaing.

He had taken service with the Emperor Maximilian I and won distinction for bravery and leadership, being appointed member to the council of Charles of Burgundy; later Emperor Charles V and his Caballerizo mayor in 1515.

Appointed knight of the Order of the Golden Fleece in 1516, he had become governor of Tournai in 1521, had been made viceroi of Naples in 1522, and is made commander in chief of Imperial armies in Italy upon the death of Prospero Colonna at the end of 1523.

The forces of Lannoy and of Gouffier clash near the Sesia River, on April 30, when the Spanish-Imperial troops intercept the French.

Bonnivet's forces (where many of the Swiss mercenaries abandon the French army) suffer a decisive defeat by Lannoy's forces.

Pierre Terrail, Lord of Bayard, after allaying a revolt at Genoa, and striving with the greatest assiduity to check a pestilence in Dauphiné, Bayard had been sent into Italy with Admiral Bonnivet, who, being defeated at Robecco and wounded in a combat during his retreat, implores Bayard to assume command and save the army.

He repulsed the foremost pursuers, but in guarding the rear at the passage of the river Sesia between the towns of Romagnano Sesia and Gattinara, is mortally wounded by an arquebus ball, another demonstration of the power of the Spanish arquebusiers against more traditional troops.

He dies in the midst of the enemy, attended by Pescara, the Spanish commander, and by his old comrade, Charles, duc de Bourbon, who is now fighting on the opposite side.

Charles is reported to have said “Ah! Monsieur de Bayard... I am very sad to see you in this state; you who were such a virtuous knight!”

Bayard answered, “Sir, there is no need to pity me. I die as a man of honor ought, doing my duty; but I pity you, because you are fighting against your king, your country, and your oath.”

His body is restored to his friends and will be interred at Saint-Martin-d'Hères.

Finally, the French army retreats into the Alps in disarray.

Charles de Lannoy launches an invasion of Provence, commanded by Don Fernando d'Avalos and Charles de Bourbon, crossing the Alps in early July with nearly eleven thousand men.

The Spanish-Imperial forces capture and sack most of the smaller towns of Provence, and finally Charles de Bourbon enters the provincial capital of Aix-en-Provence on August 9, taking the title of Count of Provence.

Fernando d'Avalos and Charles de Bourbon had by mid-August, besieged Marseille, the only stronghold in Provence that remains in French hands.

Their assaults upon the city fail, and when the French army commanded by Francis I himself arrives at Avignon at the end of September, they are forced to retreat back to Italy.

King Francis crosses the Alps in mid-October and advances on Milan at the head of an army numbering more than forty thousand men.

Bourbon and d'Avalos, their troops not yet recovered from the campaign in Provence, are in no position to offer serious resistance.

The French army moves in several columns, brushing aside Imperial attempts to hold its advance, but fails to bring the main body of Imperial troops to battle.

Nevertheless, Charles de Lannoy, who has concentrated some sixteen thousand men to resist the thirty-three thousand French troops closing on Milan, decides that the city cannot be defended and withdraws to Lodi on October 26.

Francis, having entered Milan and installed Louis II de la Trémoille as the governor at the urging of Bonnivet and against the advice of his other senior commanders, who favor a more vigorous pursuit of the retreating Lannoy) advances on Pavia, where Antonio de Leyva remains with a sizable Imperial garrison.

De Levya, belonging to a family from Navarre, had made his military debut in the Alpujarras in 1502 during the struggle against the revolting Mudéjares from Granada and later served in Italy under the Gran Capitán from 1503 to 1504.

He plays a prominent part in the Italian Wars and had been wounded at the battle of Ravenna in 1512.

Under the Marquis of Pescara, he had fought near Milan and in the unlucky campaign of Provence in 1524.

The main mass of French troops arrives at Pavia in the last days of October 1524.

Montmorency has crossed the Ticino River and by November 2 has invested the city from the south, completing its encirclement.

Inside are about nine thousand men, mainly mercenaries whom Antonio de Leyva is able to pay only by melting the church plate.

A period of skirmishing and artillery bombardments follows, and several breaches have been made in the walls by mid-November.

On November 21, Francis attemptw an assault on the city through two of the breaches, but is beaten back with heavy casualties; hampered by rainy weather and a lack of gunpowder, the French decide to wait for the defenders to starve.

A Spanish force commanded by Hugo of Moncada lands near Genoa in early December, intending to interfere in a conflict between pro-Valois and pro-Habsburg factions in the city.

Francis dispatches a larger force under Michele Antonio I of Saluzzo to intercept them.

Confronted by the more numerous French and left without naval support by the arrival of a pro-Valois fleet commanded by Andrea Doria, the Spanish troops surrender.

Francis now signs a secret agreement with Pope Clement VII, who pledges not to assist Charles in exchange for Francis's assistance with the conquest of Naples.

Against the advice of his senior commanders, Francis detaches a portion of his forces under the Duke of Albany and sends them south to aid the Pope.

Lannoy attempts to intercept the expedition near Fiorenzuola, but suffers heavy casualties and is forced to return to Lodi by the intervention of the infamous Black Bands of Giovanni de' Medici, which had just entered French service.