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Immune checkpoint inhibitor colitis is a common immune-related adverse event associated with immunotherapy and may be refractory to corticosteroids and biologic therapy. Evidence guiding management beyond anti-tumour necrosis factor and anti-integrin therapy remains limited. We report a case of severe immune checkpoint inhibitor colitis in a man in his 60s with metastatic melanoma treated with combination ipilimumab and nivolumab. Colitis was refractory to corticosteroids, dose-escalated infliximab and vedolizumab. Upadacitinib was commenced with rapid improvement, with stool frequency decreasing from 40 bowel motions per day to 6 within 24 hours. This response was accompanied by a marked decrease in C-reactive protein and faecal calprotectin. His recovery was complicated by cytomegalovirus infection, successfully treated with valganciclovir. A repeat colonoscopy demonstrated complete mucosal healing and the patient achieved durable steroid-free remission following treatment cessation. This case illustrates the potential role of Janus kinase 1 inhibition as a salvage strategy in refractory immune checkpoint inhibitor colitis.