The best advice i have for chemicals is read the label.
Round-Up will most likely get there, but there are some limits. It’s slow to act. Temperature matters. Water source and certain particulates matter. On some plants, multiple applications may be needed.
What i recall of fireweed is… there are at least three different things called fireweed depending on where you may be. The one I know of is a Senecio species. it’s a cool season grower. Best advice, keep it from going to seed. Mow, spray it, pull it, whatever. If you can manage to maintain strong turf, that alone will help reduce how it can spread. While fireweed does not exist where i am, i do have some cool season growers and turf (or pasture) weeds. Best advice…keep from going to seed, manage for healthy, vigorous turf to help reduce germination.
If you don’t have this weed, be grateful. If you are the kind who thinks what someone else calls a weed is simply a plant we haven’t learned to appreciate yet, this may be the one to use as an example to refute simplistic arguments.
As to why Round-Up may not be effective as a single application…again, read the label.
Round-Up is not a magic bullet style, one-spray-kills-all application. It’s more a one spray kills most, but certain plants it’s more of a suppressant and it takes multiple applications to reach desired die-off.
It can take time to reach full effectiveness. It’s absorbed into the plant and killed it from the inside out by inhibiting enzyme formation. It’s a process that takes time, and a process that is helped by the plant being actively growing. as such, most effective on warm sunny days where plants are actively going through all the processes of photosynthesis.
water quality can affect efficacy. specifically, colloidal clay can bind with the chemical and reduce effectiveness.
don’t take this as someone saying you don’t know what you are doing…i’m not saying that. i’m laying out ways where the active ingredient in round-up may not perform to expectations.
good luck.