Immune checkpoint inhibitors (ICIs) cause inflammatory immune-related adverse events (irAEs), which are often effectively managed with steroids. Less is known about the best management of irAEs refractory to steroid treatment. We aimed to assess the efficacy of second-line medications used to treat gastrointestinal (GI) irAEs. This study was a single-center, retrospective medical record review of patients who received steroids for an ICI GI irAE and at least one dose of infliximab, vedolizumab, or adalimumab for irAE treatment from March 25, 2011 to September 20, 2019, approved by Yale University's Institutional Review Board. Our primary objective was to assess the efficacy of second-line treatment, measured by the change in the Common Terminology Criteria for Adverse Events Version 5.0 grading system. A total of 39 patients met inclusion criteria. Treatment for steroid-refractory GI irAEs demonstrated a high response rate, with irAE resolution seen in 89.7% of patients. Patients who were specifically initiated on infliximab within 14 days of starting steroids had a higher percent resolution seen in 94.4% of patients. The average time to response, defined as the average days from second-line therapy to reported symptom resolution, was 17 days. Steroid-refractory GI irAEs can be managed effectively in most patients with immunosuppressive therapy, such as infliximab. Furthermore, initiating second-line immunosuppressive therapy within 14 days of steroid failure resulted in a higher rate of symptom resolution.