Background: The synergistic antitumour effect immune checkpoint inhibitors combined with antiangiogenic targeted therapy in refractory RM-NPC patients remains unknown. This phase 2 trial assessed the efficacy and safety of camrelizumab (an anti-programmed death 1 [PD-1] inhibitor) plus apatinib (a VEGFR-2 tyrosine kinase inhibitor) after at least first-line therapy in refractory RM-NPC patients. Methods: We did a phase 2 single-armed study to evaluate the activity of camrelizumab plus apatinib in platinum-resistant (cohort 1) and PD-1 inhibitor resistant (cohort 2) NPC. Eligibility required measurable disease (RECIST 1·1), Eastern Cooperative Oncology Group (ECOG) performance status of 0-1, age of 18-75 years, and disease progression on platinum but PD-1 inhibitor-naive (cohort 1) or disease progression on PD-1 inhibitor (cohort 2) after at least first-line therapy. Patients in cohort 1 received 200 mg intravenous camrelizumab every 3 weeks plus 250 mg oral apatinib daily. Patients in cohort 2 received apatinib monotherapy in the first two weeks to modify the immune-resistant microenvironment, and were then administered camrelizumab plus apatinib until disease progression or unacceptable toxicity. The primary endpoint was the objective response rate (ORR). This study was registered with ClinicalTrials.gov (NCT04547088, NCT04548271). Results: From August 20, 2020 to September 6, 2021, 72 patients were enrolled into the trial: 40 patients were enrolled in cohort 1 and 32 in cohort 2. Median follow-up was 13.1 months (IQR 10.0-15.2 months) for cohort 1 and 9.0 (5.9-10.7) months for cohort 2. Among the 40 evaluable patients in cohort 1, an objective response was achieved by 26 (65%; 95% CI, 49.6-80.4). A total of 16 (40%) patients had tumor progression, and the median PFS was not reached. Among the 32 evaluable patients in cohort 2, an objective response was achieved by 11 (34.4%; 95% CI, 17.0-51.8). A total of 22 (69%) patients had tumor progression, and the median PFS was 6.0 months (95% CI, 4.4 to 7.6). Grade ≥ 3 treatment-related adverse events (TRAE) were reported in 34 (47.2%) of 72 patients, with the most common TRAE being hypertension (18.1%), an increase of serum transaminase (13.9%) and hand and foot syndrome (12.5%). No treatment-related deaths occurred. Conclusions: In patients with platinum-resistant or PD-1 inhibitor resistant RM-NPC, camrelizumab plus apatinib achieved promising outcomes. Further studies of the camrelizumab plus apatinib treatment regimen are warranted in a phase 3 trial. Clinical trial information: NCT04547088, NCT04548271.