Background <p>Over the last three decades, hepatic arterial infusion (HAI) chemotherapy combined with systemic therapy has been established as a treatment strategy for patients with unresectable liver metastases. Facilitating a HAI program outside the USA and Europe remains underutilized in regions, including Israel, and requires multidisciplinary collaboration. The purpose of this study is to describe the feasibility and early outcomes of the initiation of the first hepatic artery infusion program in Israel.</p> Patients and Methods <p>This retrospective analysis was conducted at a tertiary medical center in Israel. It included 21 patients with unresectable colorectal liver metastases who underwent hepatic artery infusion port placement between February 2020 and March 2022. All participants underwent hepatic artery infusion port placement with most subsequently receiving chemotherapy. The study evaluated perioperative outcomes, complication rates, response rates, and conversion to resectability at 6 months.</p> Results <p>Hepatic arterial infusion chemotherapy was successfully administered to 95% of patients. The overall 90-day major complication rate was 24%, with no reported mortality. At 6 months, the partial response rate was 33%, and the disease control rate was 83%. Four out of five patients (80%) with neoadjuvant intent converted from unresectable to resectable during HAI treatment.</p> Conclusions <p>This study demonstrates the feasibility and safety of implementing a new HAI program for carefully selected patients with colorectal liver metastases. Despite the cohort being heavily pretreated with systemic chemotherapy, promising hepatic response rates and disease control rates were observed. These findings support the potential for expanding access to HAI therapy in new geographic regions.</p>