It would not be illegal under federal law for California to hold a referendum on secession. It wouldn't mean anything at all. It would be legally equivalent to my planting a big red flag in the turf at a National Park and claiming that land in the name of Portugal. (it's a crime - littering - if you leave the flag there when you leave) The Federal Marshals could watch if they wanted to.
A number of actions taken by the state of California after the referendum would probably be illegal under federal law, unless the people of California held the referendum and passed it and the state officials in California simply ignored it. You'd expect that to cause a constitutional crisis at the state level in California, and that might eventually bubble up to the federal courts.
If the referendum passed and the state actually started to behave independently and take liberties with federal property, all sorts of things would start to go wrong for them. You don't really need to get heavy handed with federal law enforcement in that case. Not when you control the Federal Reserve Banks and pretty much everything else. There's a whole path of escalation you could follow in the courts before federal agents would start arresting people, but even if you want to get right to that you have to wait for them to commit actual crimes.
California has, in fact, held initiatives (“referendum” has a particular meaning in California law which is slightly different than it's general usage) on things which violate the federal Constitution. The federal government has done nothing about the votes, though it has a role in challenging and overturning substantive actions taken by the State based on such initiatives after they've passed.
There's no real reason to think a secession initiative would be any different.
If, for example, the State Of California, in the US, were to organize, without constitutional mandate, an "official" referendum calling for succession, Federal Marshall would be all over that in a blink of an eye.
And I'd agree that heavy-handed action gives the Calatan separatists quite a boost ... for the short term. But states don't really have choice about enforcing the law when a significant actor is visibly flouting that law. That's just how the law works, more or less everywhere it exists.
IE, the situation is as the GP states.