Beetlejuice invents a cologne that changes the personality of anyone it comes in contact with into its polar opposite. When Lydia gets sprayed with it, she becomes a wild, prank-pulling criminal and, taking Beetlejuice along for the ride, wreaks more havoc on the Neitherworld than BJ's ever been responsible for.

Beetlejuice gets pulled into The Chromazone, a Twilight Zone spoof. There, BJ has to help Tod Sperling defeat Ima Loony, one of his creations who has begun writing her own scripts. But BJ loses his mind (literally) in the process. If Lydia can't get into the Chromozone in time, BJ will be brainless forever, not to mention vapid.