Ultraviolet (UV) water disinfection method has emerged as an alternative to chemical methods of disinfection. In typical UV photoreactors for water treatment, water flows in the space between the lamp’s sleeve and outer shell. The contact of water and sleeve causes fouling, which reduces the effectiveness of UV. To clean the photoreactor, the quartz sleeve must be replaced; this may lead to quartz or lamp breakage and mercury leakage into water during cleaning. In this study, a novel type of multi-lamp UV photoreactors is proposed, in which the UV lamps are placed out of the water channel and their UV irradiation is redirected into the channel using an outer cylindrical reflector. This allows for the installment of a self-cleaning mechanism for the water channel. A well-validated three-dimensional CFD model is utilized to model the performance of this photoreactor for microbial inactivation. The impacts of several geometrical and optical parameters are investigated on the inactivation of microorganisms. The results revealed that the difference in log reduction values (LRV) between fully specular and fully diffuse reflector ranges from 10 to 47% as the lamp-to-channel distance increases. For the volumetric flow rate of 25 GPM, the LRV of a photoreactor with fully diffuse reflector can be 46% higher than a fully specular one. In addition, the performance of the proposed photoreactor is compared against a classic L-shaped annular photoreactor. The results show that the new design can provide equal or better microbial performance compared to the classic photoreactor, but it removes many of their common issues such as quartz fouling, lamp overheating at low flow rates, and sleeve breakage during lamp replacement.