We report 5 cases in which the recurrence of colorectal cancer (CRC) presented as a mass involving the duodenum and pancreas. The treatment approach for such recurrences is not standardized, and in particular, the benefits of pancreaticoduodenectomy for such cases are not known. We describe the successful use of aggressive multimodality treatment with chemotherapy, radiation, and en bloc surgical resection. Such trimodality therapy can result in durable palliation of symptoms and long-term survival for patients with recurrent CRC involving the duodenum and pancreas, even when other metastases are present.