I have to admit I'm not sure what is being suggested. IOTL, the Kings of France did expend a good deal of effort into absorbing the Burgundian inheritance, and this involved them in war with Spain, since the Kings of Spain had inherited what remained of the Burgundian territories (or more properly, the other way around). The northeastern frontier of France was a major theater of war.
On French colonization efforts, Cartier's efforts to establish what became Quebec failed. French Canada really dates to Champlain and 1608, which is after the time period posted. The French acquired what became Haiti in 1625. The French did nothing in the fifteenth century and funded some exploration in the 17th century, as did the English incidentally.
Maybe the OP is suggesting getting rid of the French invasions of Italy, but note that this is somewhat unlikely. The French kings thought they were the rightful heirs to the Kingdom of Naples and the Duchy of Milan. Countries really didn't expand like in Rick, legal claims were really important. And the French had been deeply involved in Italy in the Middle Ages, hence the links to Milan and Naples. So this supposes that the French kings forget about their past history and claims in Italy and concentrate on the northeastern frontier. That is unlikely but doable. With no French involvement in Italy, the Spanish kings would likely not bother with Milan, though they had held Sicily since the thirteenth century and would certainly pick up Naples too, which is sort of linked ot Sicily.
The problem is that removing the link between Spain and the Burgundian inheritance creates huge amounts of butterflies. You pretty much have to give the Burgundian inheritance to some other dynasty, which means changing marriages and affecting dynasties across Europe. You could have Charles the Bold be more successful and have a maile heir, but that has unpredictable implications. You could have his daughter Mary marry Edward IV of England and not the Holy Roman Emperor Maximilian, but this changes the dynasties of both Castille and England. Maybe not have Philip marry Joanna of Castile and marry someone else, but at this point Charles VIII's invasion of Italy has already happened.
The Netherlands was as wealthy and important as northern Italy, so if the French just skipped their Italian invasions, some sort of coalition of other European powers would have emerged to stop them in the Netherlands, even if Castille and Aragon were not involved. As for the Spanish, they still have to fight the Turks in the Med, if only to contain the piracy. The biggest effect of no Burgundian connection, other than the dynastic implications, is more success in North Africa which actually does have interesting implications. The colonial empire is less affected because IOTL they did as well as they could have in that area, in fact making almost ASB generated progress.
Anything that does away with Charles V really scrambles the timelines of European history well past the 16th century.