Toxic megacolon is most commonly considered as a complication of inflammatory bowel disease, especially ulcerative colitis and colonic Crohn's disease to a lesser extent. It appears in the context of moderate-to-severe disease and often requires colectomy. Currently, after an inadequate response to conventional therapy with systemic corticosteroids, the use of cyclosporine or infliximab is considered as an alternative option, prior to surgical intervention. We present a case report of toxic megacolon in a patient with a severe refractory colonic Crohn's disease, where anti-tumor necrosis factor (anti-TNF) therapies were contraindicated. Consequently, we decided to use ustekinumab as a rescue therapy, despite insufficient evidence to provide recommendations for this indication.