While initially successful, the Imperial offensive lost valuable time during the Siege of Marseille and was forced to withdraw back to Italy by the arrival of Francis and the main French army at Avignon.

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

[9] Lannoy attempted to intercept the expedition near Fiorenzuola, but suffered heavy casualties and was forced to return to Lodi by the intervention of the infamous Black Bands of Giovanni de' Medici, which had just entered French service.

D'Avalos captured the French outpost at Sant'Angelo Lomellina, cutting the lines of communication between Pavia and Milan, while a separate column of landsknechts advanced on Belgiojoso and, despite being briefly pushed back by a raid led by Medici and Bonnivet, occupied the town.

In the ensuing four-hour battle, the French heavy cavalry, which had proven so effective against the Swiss at Marignano ten years prior, masked its own artillery by a rapid advance and was surrounded and cut apart by landsknechts and d'Avalos's massed Spanish arquebusiers.

[14] The night following the battle, Francis gave Lannoy a letter to be delivered to his mother in Paris, in which he related what had befallen him: "To inform you of how the rest of my ill-fortune is proceeding, all is lost to me save honour and life, which is safe.

[16] The broken remnants of the French forces, aside from a small garrison left to hold the Castel Sforzesco in Milan, retreated across the Alps under the nominal command of Charles IV of Alençon, reaching Lyon by March.

Charles V, lacking funds to pay for the war, decided to forgo the marriage into the House of Tudor which he had promised Henry VIII and sought instead to marry Isabella of Portugal, who would bring with her a more substantial dowry.

[19] Francis, convinced that he would regain his freedom if he could obtain a personal audience with Charles, pressed d'Avalos and Lannoy, who had intended to transport the king to the Castelnuovo in Naples, to send him to Spain instead.