The move will "force Europe to go forward, undoubtedly with different speeds", he said during a visit to Indonesia, the final stop on the last major international tour of his term in office.
Describing the procedure to exit the EU as "irreversible", Hollande stressed that it could not go beyond two years.
"It will end with a trade agreement between Great Britain and Europe, we hope that it's the best trade agreement possible, for Europe and for Great Britain," Hollande said.
While Brexit is "sentimentally painful" for the Europeans, it would be "economically painful" for the British, he added.
Hollande said, however, "it is not our intention to punish (the British) for the principle".
Weeks ahead of the French presidential election, Hollande said Brexit was "very important in the electoral debate".
Speaking of candidates pushing for France to exit the EU, he said such a move "has a cost for the country that emerges in terms of work, free circulation, finance" and "Great Britain will be forced to pay".
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