It would be wrong of us to try to insist that those who want to exit must stay, just as it is wrong for people who are seriously out of step with (and ignorant of) the rest of the country to insist that everyone else must abide by their extremely Byzantine rules and social codes.
But the land is ours. Ownership derives from permission granted by the United States of America. This can be withdrawn. What do you think the basis for eminent domain is?
Certainly, those who want to Calexit would have no problem selling their property. The California real estate market would tank, but the water situation would improve.