Italian War of 1521–1526 participant Kingdom of France
The Italian War of 1521–1526, sometimes known as the Four Years' War, (French: Sixième guerre d'Italie) was a part of the Italian Wars.  The war pitted Francis I of France and the Republic of Venice against the Holy Roman Emperor Charles V, Henry VIII of England, and the Papal States.  It arose from animosity over the election of Charles as Emperor in 1519–1520 and from Pope Leo X's need to ally with Charles against Martin Luther.
The war broke out across Western Europe late in 1521, when a French–Navarrese expedition attempted to reconquer Navarre while a French army invaded the Low Countries.  A Spanish army drove the Navarrese forces back into the Pyrenees, and other Imperial forces attacked northern France, where they were stopped in turn.
In 1521 Charles V and Henry VIII signed the Treaty of Bruges in secret against France, and hostilities resumed on the Italian Peninsula. At the Battle of Bicocca on 27 April 1522, Imperial and Papal forces defeated the French, driving them from Lombardy. Following the battle, fighting again spilled onto French soil, while Venice made a separate peace.  The English invaded France in 1523, while the French military leader Charles de Bourbon, alienated by Francis's attempts to seize his inheritance, betrayed Francis and allied himself with the Emperor.  The failure of a French attempt to regain Lombardy in 1524 provided Bourbon with an opportunity to invade Provence at the head of a Spanish army.
Francis led a second attack on Milan in 1525. His disastrous defeat at the Battle of Pavia, where he was captured by the Imperial captain Charles de Lannoy and many of his chief nobles were killed, led to the end of the war. Francis was imprisoned in the Lombard city of Pizzighettone and then in Madrid. Diplomatic maneuvers to obtain his release included a French mission sent by his mother, Louise of Savoy, to the court of Suleiman the Magnificent that resulted in an Ottoman ultimatum to Charles. This unprecedented alignment between Christian and Muslim monarchs caused a scandal in the Christian world, and laid the foundation for the Franco-Ottoman alliance. Suleiman invaded Hungary in the summer of 1526, defeating Charles' allies at the Battle of Mohács. Despite these efforts, Francis signed the Treaty of Madrid, surrendering his claims to Italy, Artois, Flanders, and Burgundy. A few weeks after his release, he repudiated the terms of the treaty, starting the War of the League of Cognac.  The Italian Wars continued for another three decades, ending with France having failed to regain any substantial territories in Italy.