In this contribution, we present a robust and efficient computational framework capable of accurately capturing the dynamic motion and large deformation/deflection responses of highly-flexible rods interacting with an incompressible viscous flow. Within the partitioned approach, we adopt separate field solvers to compute the dynamics of the immersed structures and the evolution of the flow field over time, considering finite Reynolds numbers. We employ a geometrically exact, nonlinear Cosserat rod formulation in the context of the isogeometric analysis (IGA) technique to model the elastic responses of each rod in three dimensions (3D). The Navier–Stokes equations are resolved using a pressure projection method on a standard staggered Cartesian grid. The direct-forcing immersed boundary method is utilized for coupling the IGA-based structural solver with the finite-difference fluid solver. In order to fully exploit the accuracy of the IGA technique for FSI simulations, the proposed framework introduces a new procedure that decouples the resolution of the structural domain from the fluid grid. Uniformly distributed Lagrangian markers with density relative to the Eulerian grid are generated to communicate between Lagrangian and Eulerian grids consistently with IGA. We successfully validate the proposed computational framework against two- and three-dimensional FSI benchmarks involving flexible filaments undergoing large deflections/motions in an incompressible flow. We show that six times coarser structural mesh than the flow Eulerian grid delivers accurate results for classic benchmarks, leading to a major gain in computational efficiency. The simultaneous spatial and temporal convergence studies demonstrate the consistent performance of the proposed framework, showing that it conserves the order of the convergence, which is the same as that of the fluid solver.