No, everyone doesn't 'know what it means', not without additional mental parsing. Myself, among many others, read it first as a double-negative, then have to double-take it and reinterpret it. Irrespective, irreducable, irrecoverable, irreconcilable, irrelevant, irreligious, irrefutable - irregardless stands out like a sore thumb.

Or should I say 'irreinterpret it'? After all, you would 'know what I meant' if I wrote that.

Ambiguity is fine if you're writing for poetic effect, but if you're trying to get a point across, it should be minimised.

Everybody knows that it means not (not in regard).