Real-time collision-avoidance navigation of autonomous ships is required by many application scenarios, such as carriage of goods by sea, search, and rescue. The collision avoidance algorithm is the core of autonomous navigation for Maritime autonomous surface ships (MASS). In order to realize real-time and free-collision under the condition of multi-ship encounter in an uncertain environment, a real-time collision avoidance framework is proposed using B-spline and optimal decoupling control. This framework takes advantage to handle the uncertain environment with limited sensing MASS which plans dynamically feasible, highly reliable, and safe feasible collision avoidance. First, owing to the collision risk assessment, a B-spline-based collision avoidance trajectory search (BCATS) algorithm is proposed to generate free-collision trajectories effectively. Second, a waypoint-based collision avoidance trajectory optimization is proposed with the path-speed decoupling control. Two benefits, a reduction of control cost and an improvement in the smoothness of the collision avoidance trajectory, are delivered. Finally, we conducted an experiment using the Electronic Chart System (ECS). The results reveal the robustness and real-time collision avoidance trajectory planned by the proposed collision avoidance system.