Chimeric antigen receptor T (CAR T) cells have shown their potential in hematological malignancies and the treatment of solid tumors, especially in metastases. However, CAR T-cell therapy may carry risks of inducing severe adverse effects, which are recognized as immune-related adverse events. Here, we report two cases of severe colitis presented with refractory bloody diarrhea, which were induced by carcinoembryonic antigen (CEA)-directed CAR T therapy in the treatment of metastatic colorectal adenocarcinoma. These patients were treated as part of a clinical trial. The clinical trial was registered at ClinicalTrials.gov (NCT05396300), submitted, and started on May 25, 2022. Glucocorticoids combined with vedolizumab were used to control their gastrointestinal symptoms but the outcomes were unsatisfactory. This report highlights the potentially serious risks of anti-CEA CAR T therapy and provides management options.