Purpose: For patients with unresectable colorectal liver metastasis (CRLM), transarterial embolization with the use of drug-eluting beads with irinotecan (DEBIRI) represents a novel alternative to systemic chemotherapy or local treatments alone. The present systematic review evaluates available data on the efficacy and safety of DEBIRI embolization. Materials and Methods: A comprehensive search of medical literature identified studies describing the use of DEBIRI in the treatment of CRLM. Data describing adverse events, pharmacokinetics, tumor response, and overall survival were collected. Results: Five observational studies and one randomized controlled trial (RCT) were reviewed. A total of 235 patients were included in the descriptive analysis of observational studies. Postembolization syndrome was the most common adverse event. Peak plasma levels of irinotecan were observed at 1-2 hours after administration. Wide variations in tumor response were observed. The median survival time ranged from 15.2 months to 25 months. In the RCT, treatment with DEBIRI was superior to systemic chemotherapy with 5-fluorouracil/leucovorin/ irinotecan in terms of quality of life and progression-free survival. Conclusions: For patients with unresectable CRLM, particularly after failure to respond to first-line regimens, DEBIRI represents a novel alternative to systemic chemotherapy alone, transarterial embolization with other agents, or other local treatments (eg, microwave or radiofrequency ablation). In these reports, DEBIRI was safe and effective in the in the treatment of unresectable CRLM. Further RCTs comparing DEBIRI with alternative management strategies are required to define the optimal role for this treatment.