Even though Spanish troops had helped Francesco II regain his duchy, at the time of his death in 1535, Milan was independent of both French and Spanish forces. In OTL, Francis I invaded Savoy in 1536 and I could certainly see him in TTL taking advantage of the deaths of Francesco and Charles V to invade both Savoy and Milan. As Emperor, Ferdinand I would be obliged to protect both Savoy and Milan but would be unable to regain them from France without the help of Spain. Spain would not want the French to control Milan not only to protect their access to the Netherlands but to also keep Naples from being vulnerable to French invasion. However, Isabella would likely try to avoid war during the minority of Philip II. By granting Milan to a younger son of Francis in return for Francis restoring Savoy to its rightful ruler, Ferdinand I would giving both himself and Philip II enough breathing space to deal with more immediate problems(like the Ottomans) while leaving the possibility of taking Milan back eventually.