Yeah, he and Claude had seven kids (four of those being sons), but literally only one son outlived Francis I
Francis I and Claude had four daughters and three sons. Only Henry II and Marguerite outlived Francis.
Let's say Francis gets over his hatred of Charles for the sake of his realm's succession and gets Eleanor pregnant multiple times. These would be their children:
Joanna (b. 1533)
Philip (b. 1534)
Ferdinand (b. 1536)
As it was pointed out, after Charles d'Orléans' death, Philip would immediately replace him in the application of the Treaty of Crepy. It means he would marry an Austrian archduchess and would become duke of Milan. Of course, he would also inherit most of Charles d'Orléans' French titles.
I don't know if he would become a "foe" for his half-brother Henry II but what is sure is that he would be the most powerful lord in France, in addition of being duke of Milan. As a result, he would necessarily be a prominant actor of the French Religious Wars. Of course, it is difficult to figure how he would position in these wars.
Ferdinand's fate is more uncertain.
In OTL, Catherine de Medici tried to arrange a marriage between her son the duke of Anjou (future Henry III) and the widowed Juana of Austria, with Milan or Netherlands as a dowry. Considering that, maybe Ferdinand would have the same purpose for himself: marrying Juana with Netherlands as a dowry (as Milan is already token by Philip) but, of course, Charles V and Philip II would have little to no reason to accept. Maybe Ferdinand would end up doing precisely what the duke of Alençon did in OTL: siding with Dutch rebels and being elected by them.
Another possibility for him is a rapprochement between France and Portugal and a marriage with Maria of Portugal (OTL duchess of Parma). If Portuguese succession still goes as in OTL, it may have huge consequences as Ferdinand and Maria's children would have a claim (maybe the best claim) to the Portuguese throne after the cardinal-king's death.
As for Joanna, as weird as it seems, I think there are good chances that she would marry... Edward VI.
In OTL, Edward VI was fianced to Elisabeth of France, Henry II's daughter, in 1551. At this time, Edward was 14 and Elisabeth was only 6, meaning he had to wait her to grow up. But he died before and the marriage never occured. There was, at this time, a grown up celibate princess in France: Marguerite, Henry II's sister. I guess she was not considered for Edward VI because of the age gap: she was 28 at this time, so 14 years older than him. But Joanna would be much closer in age to Edward: she would only be 4 years older. Then, I see no reason to wait Elisabeth to grow up: you can simply marry 14 years old Edward to 18 years old Joanna. And if Edward manages to impregnate Joanna before dying, English succession is not the same as in OTL. There may be a fight for regency between Joanna and Mary Tudor. Or the two may make an alliance in order to bring England back to Catholicism.