Background: The combination of bevacizumab and immune checkpoint inhibitors (ICI) has demonstrated promising efficacy and safety in the first-line treatment of advanced hepatocellular carcinoma (HCC). However, this combination has not been examined in patients with previous first-line treatment of ICI and tyrosine kinase inhibitor. This study aimed to investigate the effectiveness and safety of bevacizumab combined with atezolizumab or sintilimab as second-line treatment in patients with advanced HCC. Methods: The retrospective study included patients with advanced HCC who received combined therapy of bevacizumab and atezolizumab or sintilimab after failure of lenvatinib plus ICI between July 28, 2020 and March 7, 2022. Baseline patient characteristics were collected. Treatment response, overall response rate (ORR) and disease control rate (DCR) were evaluated according to response evaluation criteria in solid tumors (RECIST) version 1.1. Overall survival (OS) and progression-free survival (PFS) were analyzed by the Kaplan-Meier method. Treatment-related adverse events were graded according to Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0. Results: A total of 20 patients with advanced HCC were included, with a median follow-up time of 11.05 (5.03-20.63) months. Eleven patients died by the last follow-up on August 12, 2022. There were 18 males (90%) and two females (10%). The average age was 59.9±12.08 years. Seven patients (35%) had distant metastasis, and nine (45%) had vascular invasion. Liver function was classified as Child-Pugh grade A in 17 patients (85%) and grade B in three (15%). Patients with Barcelona Clinic Liver Cancer (BCLC) stages B, C and D were 1 (5%), 16 (80%) and 3 (15%), respectively. Eighteen patients (90%) had previous topical therapy. Of all patients previously administered lenvatinib plus ICI as first-line treatment, 14 (70%) had PFS longer than three months. ORR and DCR were 15% (95% confidence interval [CI], 3.2-37.9) and 55% (95% CI, 31.5-76.9), respectively. Median OS was 8.00 months (95% CI, 0.00-16.66), while median PFS was 3.80 months (95% CI, 2.41-5.19). Adverse events were observed in 14 patients (70%). Adverse events of grade 3 or worse occurred in six patients (30%). Conclusions: The combination of bevacizumab with atezolizumab or sintilimab had tolerable safety profile but poor response in the second-line treatment of HCC. Despite the satisfying efficacy as first-line therapy, this combination is not a cost-effective recommendation for advanced HCC cases who failed the first-line treatment of lenvatinib plus ICI.