OTL, the only children of François I to leave descendants were his second son (and future king of France), Henri, and his youngest daughter, Marguerite. Henri II’s legitimate male issue died out in 1589, ushering in the House of Bourbon.
Here’s where the what if/challenge comes in: Henri’s two brothers were both subject of their own marriage plans during their truncated lives (the sickly François to Mary I of England and Maria of Portugal, Lady of Viseu; and the more rambunctious Charles to Elizabeth Tudor, Maria of Spain or Anna of Austria).
Both must leave legitimate lines of descent, WITHOUT affecting the extinction of the Valois. In other words,they can live beyond their OTL death dates, but by at latest 1600, there is no other legitimate option but the Bourbons. (Personally, I think with France having Salic Law and all, this would actually be pretty easy, just let both produce a string of daughters or let any sons of theirs die young or (in Charles’ case, from inherited massive stupidity).